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c-myc 反义寡核苷酸涂层支架局部植入给药在体分布及对细胞凋亡的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2004年第6期
页码:
535-538
栏目:
基础研究
出版日期:
2004-11-01

文章信息/Info

Title:
Effects on apoiptosis and distribution of c-myc antisense ol igodeoxynucleotides in rabbits af ter local del ivery by gelatin coated platinium-iridium stent
作者:
张新霞1; 许香广1; 胡雪松1; 方卫华1; 黄建平1; 崔长琮2
1. 广东医学院附属深圳市福田人民医院心内科,广东深圳518033 ;2. 西安交通大学第一医院心内科,陕西西安710061
Author(s):
ZHANG Xin-xia1; XU Xiang-guang1; HU Xue-song1; FANG Wei-hua1; HUANG Jian-ping1; CUI Chang-cong2
Department of Cardiology ,Shenzhen Futian Hospital Affiliated of Guangdong Medical College ,Shenzhen ,Guangdong 518033 ,China
关键词:
铂-铱; 支架; 再狭窄; 局部给药;  c-myc ; 基因治疗
Keywords:
platinium-Iridium ;  stent ;  restenosis ; local drug delivery ;  c-myc ;  gene therapy
分类号:
R541. 1 　
DOI:
-
文献标识码:
A
摘要:
目的:评价c-myc 反义寡核苷酸(ASODN) 经铂- 铱合金明胶蛋白涂层支架局部应用后,药物在组织中的分布及对血管平滑肌细胞凋亡的影响。方法:将携带羧基荧光素( FAM) 标记c-myc ASODN 的国产铂2铱合金明胶蛋白涂层支架(550μg/ 支架) 置入兔颈动脉( n = 6) ,术后45 min、2 h、6 h 分别取材,荧光显微镜下观察药物在脏器中的分布。另取家兔32 只,对照组16 只置入明胶蛋白涂层支架;处理组16 只置入携带c-myc ASODN 明胶蛋白涂层 支架。术后7 、14 、30 、90 d(均n = 4) ,取置入支架血管,行组织病理学检查,观察新生内膜增殖、细胞凋亡和c-myc表达。结果:给药后镜下观察药物主要分布于靶点血管。处理组平均新生内膜厚度与新生内膜面积均较对照组小(均P < 0. 01) 。术后30 d 在新生内膜中观察到明显的细胞凋亡,90 d 时单位面积内凋亡细胞数显著高于30 d ;同时,处理组VSMC 的凋亡数显著高于对照组。对照组新生内膜中c-myc 蛋白免疫组化及原位杂交均为阳性,处理组术后7 、14 d 为阴性,30 、90 d 为弱阳性。结论:明胶蛋白涂层支架介导的局部给药简便、可行。c-myc ASODN 在体导入后,抑制VSMC 增殖,诱导VSMC 凋亡。
Abstract:
AIM: To assess tissue dist ribution and effect on vascular smooth muscle cells (VSMCs) apoptosis of c-myc antisense ligodeoxynucleotides (ASODN) local delivery by gelatin coated Platinium-Iridium ( Pt-Ir ) stent . METHODS: Gelatin coated Pt-Ir stent absorbed FAM ( caroboxyfluo-rescein-5-succimidyl ester ) labeled c-myc ASODN (550μg per stent) were implanted into the right carotid arteries of 6 rabbit s under vision. The samples were obtained at 45 min、2 h and 6 h. Tissue dist ribution of c-myc ASODN was assessed by fluorescence microscopy. Take another 32 rabbit s , the first group was implanted gelatin coated Pt-Ir stent , the second group was implanted gelatin coated stent absorbed c-myc ASODN ( n = 16 ,respectively) . 7 、14 、30 and 90 days ( n = 4 ,respectively) after the stenting procedure , the stented segment s were harvested ,histopathology for elvaluating neointimal proliferation ,VSMCs apoptosis and c-myc expression were performed. RESULTS :FAM labeled c-myc ASODN was most intense in target vessel. Morphomet ric analysis showed that the value of neointimal area and mean neointimal thickness was less in the second group than in the first group ( P < 0. 01 , respectively) . The apoptotic cells occurred in the neointima 30 and 90 days after stenting , and the number of apoptotic cells were less at 30 days than at 90 days. Meanwhile c2myc ASODN induced more apoptotic cells than the first group. c-myc expression was positive in the first group and negative or weak positive in c-myc ASODN t reated group by ISH and immunohistochemical methods. CONCLUSION: Gelatin coated Pt-Ir stent mediated local delivery of c-myc ASODN is feasibility. c-myc ASODN can inhibit VSMC proliferation and induce VSMCs apoptosis after local delivery in vivo.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2004-3-3
更新日期/Last Update: 2004-11-01